Angiogenesis is involved in many pathological and physiological processes and is mainly driven by hypoxia. Karyopherin subunit alpha 2 (KPNA2), a member of the nuclear transport protein family, was ...recently shown to be induced by hypoxia in various types of tumours, so we aimed to investigate the role and mechanism of KPNA2 in angiogenesis under hypoxia.
After overexpression or knockdown of KPNA2 in human umbilical vein endothelial cells (HUVEC) by adenovirus vector infection, the tube formation, proliferation and migration of HUVEC under hypoxia were detected by tubule formation assay, 5-ethynyl-2'-deoxyuridine (EdU) staining and Transwell assay, respectively. After overexpression or knockdown of KPNA2 in a murine hindlimb ischemia model by local injection of purified adenovirus vector into the gastrocnemius muscle, blood flow changes were examined with a laser Doppler system. Changes in KPNA2-binding proteins under hypoxia were detected by immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP). The effect of KPNA2 on signal transducer and activator of transcription 3 (STAT3) was detected by Western blotting and quantitative RT‒PCR.
KPNA2 was upregulated in the HUVEC hypoxia model and murine hindlimb ischemia model. Overexpression of KPNA2 increased the proliferation, migration and tube formation of HUVEC under hypoxia, while knockdown of KPNA2 reduced the proliferation, migration and tube formation of HUVEC. Overexpression of KPNA2 promoted the restoration of blood flow in the murine hindlimb ischemia model, while knockout of KPNA2 inhibited the restoration of blood flow in the murine hindlimb ischemia model. Mechanistically, hypoxia promoted the binding of STAT3 to KPNA2. Overexpression of KPNA2 promoted STAT3 phosphorylation and then upregulated vascular endothelial growth factor (VEGF) and angiopoietin 2(ANGPT2), whereas knockdown of KPNA2 inhibited STAT3 phosphorylation and then downregulated VEGF and ANGPT2.
Our study demonstrates that hypoxia promotes the binding of STAT3 to KPNA2 and KPNA2 promotes angiogenesis under hypoxia by promoting the binding of STAT3 and JAK1 and regulating STAT3 phosphorylation.
Polyaniline-poly(styrene sulfonate) (PAn-PSS) hydrogels have been synthesized via supramolecular self-assembly between positively-charged PAn chains and negatively-charged PSS chains. Phase diagram ...is plotted to systematically investigate the gelation conditions for the PAn-PSS system. A hierarchical porous microstructure consisting of oriented 1D nanofibers is observed in the hydrogels, and the phase structure, molecular structure and crystal structure are also characterized. Based on the investigation of a unique transformation of the hydrogels to colloidal particles in alkaline solutions, the electrostatic interaction is proposed to be the origin force for the gelation of the materials. Additionally, in comparison with conventional PAn-PSS colloids, as-prepared PAn-PSS hydrogels are demonstrated to possess improved capacitance performance, such as higher energy density, higher power density and better electrochemical stability. The present study gives valuable hints for achieving controlled fabrication of supramolecular materials with designed structures and outstanding properties.
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With the development of nanomedicine technology, stimuli-responsive nanocarriers play an increasingly important role in antitumor therapy. Compared with the normal physiological environment, the ...tumor microenvironment (TME) possesses several unique properties, including acidity, high glutathione (GSH) concentration, hypoxia, over-expressed enzymes and excessive reactive oxygen species (ROS), which are closely related to the occurrence and development of tumors. However, on the other hand, these properties could also be harnessed for smart drug delivery systems to release drugs specifically in tumor tissues. Stimuli-responsive nanoparticles (srNPs) can maintain stability at physiological conditions, while they could be triggered rapidly to release drugs by specific stimuli to prolong blood circulation and enhance cancer cellular uptake, thus achieving excellent therapeutic performance and improved biosafety. This review focuses on the design of srNPs based on several stimuli in the TME for the delivery of antitumor drugs. In addition, the challenges and prospects for the development of srNPs are discussed, which can possibly inspire researchers to develop srNPs for clinical applications in the future.
Purpose/Significance The development of open science still faces many data ethical problems, and there is an urgent need to explore the ethical guidelines for data handling that are compatible with ...the open science innovation ecology. The establishment of ethical guidelines is essential to create a favorable open science innovation ecology for data handling that match the construction of open science innovation ecology, and guide the participants in the open science innovation ecology to act in accordance with legal regulations and ethical norms in the process of data creation, sharing, dissemination, and utilization, and restraining data handling behaviors for the good and benefit of society. Method/Process This study first uses literature research and content analysis, based on relevant laws, guidelines, draft frameworks, policies and typical data management models on data handling ethics, from a universal perspective, based on the practice of data acquisition, storage, management, use and destruction,
Curcumin could inhibit periprosthetic osteolysis induced by wear debris and adherent endotoxin, which commonly cause prosthesis loosening and negatively influence the long-term survival of joint ...arthroplasty. However, its limited water solubility and poor stability pose challenges for its further clinical application. To address these issues, we developed curcumin liposomes for intraarticular injection, as liposomes possess good lubricant capacity and pharmacological synergy with curcumin. Additionally, a nanocrystal dosage form was prepared to enable comparison with the liposomes based on their ability to disperse curcumin effectively. A microfluidic method was used for its controllability, repeatability, and scalability. The Box-Behnken Design was employed to screen the formulations and flow parameters, while computational fluid dynamics was used to simulate the mixing process and predict the formation of liposomes. The optimized curcumin liposomes (Cur-LPs) had a size of 132.9 nm and an encapsulation efficiency of 97.1%, whereas the curcumin nanocrystals (Cur-NCs) had a size of 172.3 nm. Both Cur-LPs and Cur-NCs inhibited LPS-induced pro-inflammatory polarization of macrophages and reduced the expression and secretion of inflammatory factors. The mouse air pouch model further demonstrated that both dosage forms attenuated inflammatory cell infiltration and inflammatory fibrosis in subcutaneous tissues. Interestingly, the anti-inflammatory effect of Cur-LPs was more potent than that of Cur-NCs, both in vitro and in vivo, although the cellular uptake of Cur-NCs was quicker. In conclusion, the results demonstrate that Cur-LPs have great potential for the clinical treatment of inflammatory osteolysis and that the therapeutic effect is closely related to the liposomal dosage form.
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•Curcumin liposomes were used to treat post-arthroplasty inflammatory osteolysis due to physical and pharmacological synergy.•Curcumin liposomes and curcumin nanocrystals were compared for the therapeutic effect in vitro and in vivo.•97% encapsulation efficiency of curcumin was achieved by microfluidic method and the mixing process was simulated by CFD.
Non-small cell lung cancer (NSCLC) is the common type of lung cancer, which is the leading cause of cancer death throughout the world. Most patients were diagnosed too late for curative treatment. ...So, it is necessary to develop a minimal invasive method to identify NSCLC at an early stage. In recent years, cell-free circulating tumor DNA (ctDNA) has attracted increasing attention as a potential tumor marker for its minimal invasive, convenient, and easily accepted properties. The amount of ctDNA in plasma or serum was significantly higher in NSCLC patients than that in healthy controls or patients with benign diseases. Furthermore, many studies have proved an association among tumor stage, tumor grade, lymph node involvement, the number of metastatic sites, tumor response, survival outcome, and the ctDNA levels. Many genetic changes, such as gene mutation, loss of heterozygosity, microsatellite instability, and gene methylation were also found in ctDNA in NSCLC patients. These findings demonstrated that the ctDNA could serve as a viable tool to monitor NSCLC and prompted us to find more sensitive and specific biomarkers for clinical practice, especially monitor these cases with at least one known gene abnormality. Here, we reviewed the evidence of ctDNA in NSCLC and consider possible future applications in patient management.
To investigate the wall cooling of the thrust chamber in an engine, two film-cooling structures, namely, a circular hole structure and a slot structure, were designed. Numerical simulations were ...performed to study the coupled flow and regenerative cooling heat transfer in thrust chambers with different structures. The influences of parameters such as the film mass flow rate and film hole size on wall cooling were analyzed. Experiments were conducted in a thrust chamber to validate the accuracy of the numerical calculation method. The results indicate that the slot-structured film adheres better to the wall than the circular-hole-structured film, and the film closely adhering to the wall provides better insulation against hot gas, resulting in a reduction of approximately 6% in wall temperature. When the film hole size changes, the change in circumferential wall temperature in the upstream region of the slot-structured film is more pronounced. This paper aims to provide a reference for the design of the cooling structure at the head of the thrust chamber in engineering and suggests directions for optimization and improvement.
Abstract
Prolonged parenchymal cell death leads to activation of fibrogenic cells and extracellular matrix accumulation and eventually liver fibrosis. Autophagy, a major catabolic process of ...intracellular degradation and recycling, participates in hepatic fibrosis. However, the precise role of autophagy in the pathogenesis of hepatic fibrosis is controversial. The present study aims to investigate the key role of small VCP/p97 interacting protein (SVIP) against CCl
4
-induced hepatic fibrosis via activating autophagy. Autophagy could be activated by SVIP in HepG2 cells, but starvation cannot increase SVIP expression in vitro and in vivo. Moreover, SVIP expression, in agreement with autophagic activity and the volume of lipid droplets, first increases and then decreases during the progression of liver fibrosis with CCl
4
treatment in vivo and in vivo. Further, overexpression of SVIP can protect HepG2 cells from the toxicity of CCl
4
, which could be enhanced by starvation. Finally, starvation keeps SVIP and autophagy at such high levels in the rat livers that markedly delays the progress of hepatic fibrosis. Probably, the protective effect of SVIP is associated with stabilizing nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) and transcription factor EB (TFEB). The current study provides insight into the biological role of SVIP and autophagy in regulating hepatic fibrosis, targeting SVIP might be a novel therapeutic strategy in the future.
Polyurethane elastomers with covalent adaptable networks (PU-CANs) based on the dynamic urethane bond have attracted remarkable attention owing to their reprocessability, adaptability, and ...self-healability. However, it is still a formidable challenge to achieve excellent dynamics at low temperatures since the urethane bond energy is usually high. Herein, a fluorinated phenolic polyurethane (FPPU) elastomer with CANs based on phenol-carbamate bonds was successfully designed and prepared. Subsequently, the effects of fluorine atoms on the mechanical properties, thermal stability, reprocessability, and self-healability, surface free energy, and hydrophobicity of the prepared elastomers were systematically investigated. The FPPU elastomer showed notch-insensitivity, remarkable self-healable efficiency (98%), low dynamic dissociation temperature (60°C), excellent reprocessability, and low surface energy (62 MJ m
−2
) compared with non-fluorinated counterpart phenolic polyurethane elastomer (APPU). Based on the above-mentioned features, FPPU was selected as an elastic substrate to assemble into a triboelectric nanogenerator (TENG) to harvest energy from natural motion. This TENG exhibited an excellent electrical output performance with a peak open-circuit voltage of 103 V, a peak short-circuit current of 4.7 µA and a peak short-circuit charge of 43 nC. In addition, the TENG possessed high self-cleaning and reprocessing efficiency. Furthermore, a stretchable and self-healing composite conductor based on FPPU was fabricated for flexible electronic devices.
Engineering construction in mountainous areas is a key factor inducing slope failure, which poses severe threats to life and property safety during construction and operation. Thus, clear ...understanding of slope structure and potential failure mechanisms is of great importance for slope reinforcement. The Shangge landslide, located in a mountainous area of Western Henan, China, was triggered by excavation along a toll station. The slope was still unstable after a row of anti-sliding piles were constructed. To clarify the deformation characteristics and failure mechanism of this landslide and provide reinforcement guidance for slopes with similar geological conditions, a combined method of field investigation, displacement monitoring, and numerical simulation was employed. The results indicate that the natural slope comprises a dual structure of soil and rock, and that the soil, with poor permeability and high water moisture, was prone to form a potential sliding surface. Secondly, slope excavation was the direct triggering factor. Lastly, but most importantly, the preliminary investigation work failed to accurately expose the potential position of the sliding surface, and the existing anti-slide piles failed to cross the potential sliding surface, which made them unable to effectively improve slope stability. The numerical simulation verified that the recommended piles installed on the platform of level 2 could significantly improve slope stability. Therefore, when carrying out engineering slope design in similar geological environments, the slope structure and material composition should be fully identified, and the influence of groundwater on the slope stability state should be emphasized. These results can provide a reference for similar slope reinforcement designs.
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